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-Structure paper
| タイトル | Structural basis of herpesvirus helicase-primase inhibition by pritelivir and amenamevir. |
|---|---|
| ジャーナル・号・ページ | Sci Adv, Vol. 11, Issue 45, Page eadz1989, Year 2025 |
| 掲載日 | 2025年11月7日 |
著者 | Andrey G Baranovskiy / Qixiang He / Yoshiaki Suwa / Lucia M Morstadt / Nigar D Babayeva / Ci Ji Lim / Tahir H Tahirov / ![]() |
| PubMed 要旨 | Widespread herpesvirus infections are associated with various diseases. DNA replication of human herpes simplex virus type 1 (HSV-1) requires a helicase-primase (HP) complex of three core proteins: ...Widespread herpesvirus infections are associated with various diseases. DNA replication of human herpes simplex virus type 1 (HSV-1) requires a helicase-primase (HP) complex of three core proteins: UL5, UL52, and UL8. This complex unwinds viral DNA and synthesizes primers for DNA replication, making it an attractive antiviral target. Although HP inhibitors pritelivir and amenamevir were identified through screening, their binding mechanisms remain unclear. Here, we report cryo-electron microscopy structures of HSV-1 HP bound to a forked DNA template alone and in complex with pritelivir or amenamevir. The structures reveal a bilobed architecture highlighting HP coordinated action at the replication fork and providing a structural basis for HP inhibition by illustrating precisely how pritelivir and amenamevir block helicase activity. Data lay a solid foundation for the development of improved antiviral therapies. |
リンク | Sci Adv / PubMed:41202142 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.86 - 3.43 Å |
| 構造データ | ![]() EMDB-49560: Consensus map of HSV-1 helicase-primase in complex with a forked DNA and amenamevir ![]() EMDB-49561: Focused map of UL5-UL52 (C-terminal and N-terminal) of HSV-1 helicase-primase in complex with a forked DNA and amenamevir ![]() EMDB-49562: Focused map of UL8-UL52(410-893) of HSV-1 helicase-primase in complex with a forked DNA and amenamevir EMDB-49563, PDB-9nn2: ![]() EMDB-49582: Consensus map of HSV1 helicase-primase in complex with a forked DNA ![]() EMDB-49583: Focused map of UL5-UL52 (C-terminal and N-terminal) of HSV-1 helicase-primase in complex with a forked DNA ![]() EMDB-49584: Focused map of UL8-UL52 (410-893) of HSV-1 helicase-primase in complex with a forked DNA EMDB-49585, PDB-9nnp: ![]() EMDB-49586: Consensus map of HSV-1 helicase-primase in complex with a forked DNA and pritelivir ![]() EMDB-49587: Focused map of UL52-UL5 (C-terminal and N-terminal) of HSV-1 helicase-primase in complex with a forked DNA and pritelivir ![]() EMDB-49588: Focused map of UL8-UL52 (417-890) of HSV-1 helicase-primase in complex with a forked DNA and pritelivir EMDB-49669, PDB-9nqp: |
| 化合物 | ![]() PDB-1bxd: ![]() ChemComp-ZN: ![]() ChemComp-HOH: ![]() PDB-1bxb: |
| 由来 |
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キーワード | Transferase/Hydrolase / DNA replication / HSV-1 helicase-primase / VIRAL PROTEIN / Transferase-Hydrolase complex / Transferase/Hydrolase/DNA / Transferase-Hydrolase-DNA complex / VIRAL PROTEIN/DNA / VIRAL PROTEIN-DNA complex |
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human alphaherpesvirus 1 strain 17 (ヘルペスウイルス)
homo sapiens (ヒト)
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